This is a request for an ADAMHA RSDA Level II. During the fourteen years since receiving my Ph.D., my research has focused on the identification of pathways through which environmental and psychosocial stressors, and social supports influence behavior, psychological distress and physical health. My current work addresses the possible influences of stress and support on the etiology of disease. The goal of this work is to develop and test sophisticated psycho-biologic models of the etiologic role of psychosocial factors in disease pathogenesis; in particular in relation to upper respiratory infection (URI), and to coronary heart disease (CHD). The purpose of the proposed award is to allow sufficient time to accomplish several goals: (a) the acquisition of additional knowledge in regard to the biologic processes that may mediate the links between psychosocial factors and URI, and psychosocial factors and CHD, (b) the development of sophisticated models of the psycho-biologic pathways linking stress and support to each of these diseases, (c) the pursuit of research goals in regard to testing the URI models, and ultimately the CHD models, and (d) the acquisition of statistical skills necessary to appropriately test the validity of hypothetical psycho-biologic pathways. The proposed empirical work is a prospective study of the influences of stress and social support on susceptibility to URI. A variety of measures of stress and social support are collected from healthy subjects who are subsequently inoculated with a cold or influenza virus (or placebo). The primary outcomes are assessed for four days following inoculation and include: infection (virus shedding), physical symptoms (quantity of nasal secretion), and behavioral symptoms (symptom reporting, use of handkerchiefs). The combination of a prospective design and the manipulation of the infectious agent allow us to focus on the onset of infection, eliminate the possibility that stress or support result in selective exposure to the infectious agent, and reduce the probability that association are attributable to the illness causing shifts in stress or support. Preinoculation measures of health behaviors, psychologic states, and immune status, and immune-response to the viral challenge, are assessed as indicators of possible pathways through which psychosocial factors influence infection and symptomatology.